1. Field of the Invention
The present invention relates to a method for the prevention of glucocorticoid-induced skin atrophy by the topical administration of retinoids.
2. Description of the Prior Art
The most widely prescribed drugs to treat dermatologic disease are glucocorticosteroids. Approximately 50% of prescriptions written by dermatologists are for topical glucocorticosteroids. Since the introduction of these substances in the early 1950's for dermatologic disease, topical corticosteroid therapy continues to be the mainstay for the management of a broad spectrum of inflammatory dermatoses. Although systemic corticosteroids are often required in some dermatologic diseases, topical treatment is preferred in most responsive cases because it causes fewer systemic adverse effects.
Topical corticosteroids are generally most effective in the treatment of acute and chronic dermatoses such as seborrheic or atopic dermatitis, contact dermatitis of the irritant or allergic type, localized neurodermatitis, anogenital pruritus and psoriasis.
Individual topical corticosteroid preparations vary in anti-inflammatory potency and clinical efficacy. Therapeutic efficacy of a particular steroid can often be enhanced by increasing the concentration or by using occulsive dressings. Topical corticosteroids may be grouped accoding to relative anti-inflammatory potency. Still activity may vary considerably depending upon the vehicle, the site of application, disease, the individual patient, and whether or not an occlusive dressing is used.
Although some dermatoses may require therapy with a potent corticosteroid initially, treatment with hydrocortisone, betamethasone, dexamethasone, methylprednisolone, or prednisolone, is often sufficient and is less likely to cause adverse reactions. Although fluorinated corticosteroids are generally potent and efficacious, fluorination is not essential for increased anti-inflammatory potency (e.g., hydrocortisone valerate has greater anti-inflammatory activity than does betamethasone or dexamethasone). Potent corticosteroids are customarily used for severe or resistant dermatoses such as psoriasis and chronic neurodermatitis. Dermatoses such as discoid lupus erythematosus, lichen planus, granuloma annulare, and psoriasis of palms, soles, elbows and knees or psoriatic plaques usually require potent corticosteroids.
In general, topical application of corticosteroids does not produce systemic side reactions, although abnormal laboratory tests may occur, viz., decreased adrenal production of cortisol. However, systemic corticosteroid side effects may occur when the drugs are used on large areas of the body, for prolonged periods of time, with an occlusive dressing, and/or in infants and children. These include Cushing's disease, acne, osteoporosis, etc.
Potent topical corticosteroids often cause dermatologic side effects. These are most likely to occur in intertriginous and facial areas and are most severe with fluorinated corticosteroids, especially on the face where steroids are rapidly absorbed. Local corticosteroid side effects occur most frequently with occlusive dressings, especially with prolonged therapy.
Local side effects have become more frequent with the clinical use of newer and more potent glucocorticosteroidal analogs. The most common adverse reaction is skin atrophy, i.e., a thinning of the epidermis and dermis accompanied by telangiectasia and striae. Minimal trauma to atrophic skin may also produce purpuric lesions. Other dermatologic side effects include acneiform eruption, pruritus, hypertrichosis, rosacea-like eruptions on the face, perioral dermatitis, burning or stinging sensation, folliculitis, and hypopigmentation. Skin ulceration has occurred in patients with impaired circulation. Because of the high prevalence and seriousness of skin atrophy, it would be very valuable to have available a preparation which was anti-inflammatory but did not cause skin thinning or striae; the latter is a permanent scar.
Topical retinoids such as tretinoin (all-trans-retinoic acid) have been used by dermatologists for almost twenty years. For example, tretinoin is used topically in the treatment of acne vulgaris, primarily grades I-III, in which comedones, papules, and pustules predominate.
In concentrations of 0.1% to 0.3%, tretinoin has been used successfully in the treatment of other skin conditions such as psoriasis, ichthyosis congenita, Darie's disease, epidermolytic hyperkeratosis, senile comendones, senile keratosis, trichostasis, flat warts and basal cell carcinomas.